AUCTORES
Globalize your Research
Case Report | DOI: https://doi.org/10.31579/2690-8794/084
1 Department of Medicine, Melaka Manipal Medical College, Melaka 75150, Malaysia.
2 Oncohematologist, Cancer Center of Guam, Tamuning, GU 96913, USA
*Corresponding Author: Mra Aye, Department of Medicine, Melaka Manipal Medical College, Melaka 75150, Malaysia.
Citation: Aye M., Cabot J. (2021) Case report of a Rare Cause of Portal Hypertension. Clinical Medical Reviews and Reports. 3(6); DOI: 10.31579/2690-8794/084
Copyright: © 2021, Mra Aye, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 03 May 2021 | Accepted: 19 June 2021 | Published: 13 August 2021
Keywords: william-beuren syndrome, portal hypertension
Williams or Williams-Beuren (WBS) is a developmental disorder with multisystemic manifestations. Chromosome 7 microdeletion underlying WBS occurs because of the unique genetic architecture in this region. Facial features change from subtle to dramatic. The extent of mental and development problems is variable. Cardiovascular, endocrine, and nervous system involvement mostly affect the morbidity and mortality. Although many systems are involved in this syndrome, portal hypertension and splenomegaly are scarcely reported. We report a case of William syndrome with moderate splenomegaly and portal hypertension.
Williams or Williams-Beuren syndrome (WBS) syndrome is estimated to occur in approximately 1 in 10,000 persons. [1] It is characterized by distinctive facial features, mental disability with unique personality features. It is caused by deletion of the WBS chromosome region, spanning 1.5 million to 1.8 million base pairs and containing 26 to 28 genes [1]. Exactly how gene loss leads to the characteristic phenotype of WBS is unknown, but hypo expression of gene products is likely to be involved. It is caused by haploinsufficiency for genes deleted in chromosome band 7q11.23[1]. However, apart from arterial stenoses caused by haploinsufficiency for the elastin gene (ELN) no specific implication of any other gene in the phenotype has been established reported by Miguel Del Campo Casanelles et al [2].
Recognition of WBS syndrome usually starts with the astute clinician. Clinical diagnostic criteria [3,4] have only modest usefulness as compared with rapid and accurate laboratory testing. Fluorescence in situ hybridization (FISH) involving ELN-specific probes establishes the diagnosis of WBS by showing the presence of a single ELN allele only rather than two alleles. Multisystem manifestations such as development and cognition, auditory and ear, nose, and throat, cardiovascular, dental, endocrine, gastrointestinal, genitourinary musculoskeletal, neurologic, ophthalmologic, skin and integument, personality, behavior, and emotional well-being, skin, and integument and miscellaneous are reported. Widespread gastrointestinal manifestation such as colic, difficulty feeding, textured-food intolerance constipation gastroesophageal reflux abdominal pain of unclear cause, diverticulitis can occur in young adults rectal prolapse and celiac disease was reported. However, hepatobiliary manifestations of splenomegaly, portal hypertension and rupture esophageal varices are not mentioned [1,5]. Miguel Del Campo Casanelles et al [2] reported two patients with portal hypertension leading to splenomegaly and pancytopenia carrying the common 1.5 Mb WBS deletion. They proposed this is an additional severe vascular complication of ELN deficiency and discussed the specific characteristics of the portal venous tract that could explain the impact of ELN deficiency in that venous territory.
Our aim is to report a case of WBS with portal hypertension which is so far very rare in the world literature.
A 21-year-old male was admitted for viral fever syndrome. He is a known case of William syndrome with manifestations of characteristic facial and dental features, poor cognitive function, hypertension, reflux esophagitis, portal hypertension complicated by esophageal varices and rupture and cryptogenic cirrhosis, adenotonsillar hypertrophy, obstructive sleep apnea, dental caries, and repeated otitis media. History by his mother reveals that he is the last child of her four children. Family history was unremarkable. Pregnancy and delivery at 42 weeks were uneventful. He had delayed milestones compared to her other children and was difficult to be fed. Initially he was diagnosed as Noonan’s syndrome during medical check- up when he went for hernia operation at age of 2 month. However, at age of 5 month a diagnosis of William syndrome was confirmed by genetic study. She was not sure whether FISH and molecular studies were carried out and she was unable to mention the result of genetic study result in detail. She mentioned that he had one episode of hypercalcemia in his infancy. At age of 2 he underwent emergency laparotomy when he developed abdominal pain and hematemesis, but postoperative diagnosis was intestinal obstruction.
Because of poor cognitive function, he needed to go to special school. He is dependent for all daily activities till the day of admission. At age of 5 he was diagnosed with severe esophageal reflux disease and young hypertension. However, they were informed that he has no heart disease. A few months later he developed hematemesis and melena and medical evaluation revealed ruptured esophageal varices and banding was done. Since then, he has had been doing regular check- up under hepatobiliary unit of at a tertiary hospital and ligation was done whenever it was necessary. The mother also mentioned that his platelet count is always lower than normal range. His last Esophago-Gastric-Duodenal-Scope was in Dec: 2018. He has repeated attacks gingivitis and dental caries, otitis media and nasal blockage due to Aden tonsillar hypertrophy with obstructive sleep apnea [but defaulted the investigations for obstructive sleep apnea, gingivitis secondary to bad dental caries and feeding disorder: he only eats semisolid food.
On examination, he was very friendly and cheerful. He had facial features of broad forehead, short nose and full cheeks and dental features of small or unusually shaped primary teeth and malocclusions, shown in [figure 1] consistent with William syndrome.
His height is 140cm. His limbs were shorter than his trunk. He walked, bathed, ate, and dressed in aids. His mental age was about age of 5 despite chronological age was 22. His BP was 145/85 mmHg. Systemic examination was normal [ no features of supravalvular aortic stenosis] except splenomegaly that extended 7 cm below the costal margin and very smooth skin texture. There was no clubbing of fingers, palmer erythema, spider nevi and gynecomastia and caput medusae, no ascites and edema of the legs.
Laboratory report. Full blood count: Hemoglobin 14.9g/dL, RBC 3.5x106/µL, WBC 3.5x103/µL, Platelet 42.6 x103/µL. BUSE: Sodium was 137, K 3.8, Chloride 106, HCO3 - 22 mmol/L. RP: urea is 36mmol/L and Creatinine is 63umol/L. Liver function test reveals total bilirubin of 33 umol/dl, total protein 66 where albumin is 38 and globulin is 28g/dL, Alkaline phosphate, Alanine amino aspartate and Alanine aminotransferase are 65, 81 and 43 IU/L respectively. Prothrombin time and APTT are 14 and 14.3 seconds respectively and INR is 1.24.
Echocardiogram report: Ejection fraction 74% No LVH. No RWMA, Dilated LA size, all valves morphology appeared normal, No clot, no pericardial effusion.
Ultrasonography report of liver and hepatobiliary system:
Liver is coarse in echotexture with slightly irregular margin. No focal liver lesions. Liver span measures 10.9cm. Gallbladder is well defined. No gallstone. Intrahepatic duct and common bile duct are not dilated. No intraduct calculus seen. Portal vein is patent (1.1cm). Pancreas is obscured by bowel gas. Spleen is enlarged but homogenous (18.7cm). No focal lesion. Both kidneys are normal in size and in echogenicity. BPL/PT right kidney: 9.4/1.cm: left kidney: 10.7cm/1cm No focal renal lesion or obvious calcifications. No renal calculus or hydronephrosis bilaterally. Urinary bladder is partially distended. No obvious bladder stone or mass
Impression: Liver cirrhosis with hepatosplenomegaly
This case is author’s first ever experience of William’s syndrome [1] with portal hypertension and rupture esophageal varices in 35 years as a general physician. Short stature, smooth skin, peculiar personality, poor cognitive functions, and poor dentition and associated with systemic involvement strike us a likely case of syndromic disease. However, we were unable to arrive at the diagnosis of WBS [1] unless we are informed by the mother. He has most of reported the features of WBS except its common feature of supravalvular aortic stenosis. Additionally, WBS with portal hypertension and splenomegaly and upper GI bleeding due to esophageal rupture is scarcely reported in the world literature. So far, two cases were reported by Miguel Del et al [2]. Those cases were reported to carry the common 1.5 Mb WBS deletion which were proposed to be associated with additional severe vascular complication of Elastin gene deficiency and discuss the specific characteristics of the portal venous tract that could explain the impact of Elastin gene deficiency in that venous territory.
Patients with WBS need lifelong medical attention as there are many manifestations with poor morbidity and mortality. A formal assessment of the life expectancy associated with WBS is lacking. One study of approximately 300 patients, 1 to 55 years of age, with WBS showed a cardiovascular-associated mortality 25 to 100 times that among the controls [6]. Cardiovascular manifestations are detected in about 75% of confirmed patients during their lifetime [7]. Supravalvular aortic stenosis (SVAS) is most common, peripheral pulmonic stenosis being next in frequency. Cardiovascular complications such as biventricular outflow obstruction, biventricular hypertrophy, or stenosis or occlusion of coronary ostia has been reported to increase the relative risk of adverse outcomes. Cardiovascular complications are the major cause of death in patients with WBS [8]. Vessel occlusions either arterial or venous territories are result of elastin gene deficiency [2]. Coronary artery occlusion and ventricular hypertrophy are risk factors for sudden deaths due to cardiac arrhythmias.
Fortunately, our patient has no cardiovascular involvement except hypertension and hypertensive heart disease. Hypertension is a manageable disease. However, our patient has portal hypertension and splenomegaly complicated by rupture esophageal varices. Nevertheless, he does not have signs of cirrhosis of liver both clinically and biochemically except thrombocytopenia and leucopenia in full blood picture and hyperechogenic liver in the ultrasound of liver. It can be explained by prehepatic of portal hypertension supporting the proposal by Miguel Del Campo Casanelleset et al [ 2] that portal hypertension may be an unusual complication in WBS related to the generalized dysplasia of the vascular wall of portal vein territory caused by elastin haploinsufficiency.
WBS with moderate splenomegaly complicated by pancytopenia and septic shock and death are also a major risk factors to shorten the lives of William syndrome [2] are scarcely reported which our patient has and therefore portal hypertension and splenomegaly should also be looked for in any patient diagnosed with WBS. Their two patients with portal hypertension were carrying the common 1.5 Mb WBS deletion. The great majority of patients show very similar 1.5 Mb heterozygous deletions that arise because of unequal crossing-over between highly homologous regional segmental duplications and include at least 25 identified genes [9-11].
While haploinsufficiency for the elastin gene is known to be the cause of the vascular stenoses, the other features of WBS have not been clearly attributed to specific genes and they proposed that this is an additional severe vascular complication of ELN deficiency [2].
Portal hypertension complicated by rupture esophageal varices, splenomegaly and hypersplenism are potentially lethal and should thus be looked for in any patient with WBS and splenomegaly.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
